Stroke is one the most devastating and prevalent diseases, but efforts to limit the amount of tissue damaged in the acute phase have been disappointing, highlighting the need for effective therapeutic interventions after neurological damage has occurred. A major goal of the research in stroke rehabilitation is to harness the capacity of the brain to reorganize after neurological damage has occurred and thus ultimately lead to successful recovery of function. Data from animal and human models have suggested that sensory input plays an important role in motor output, possibly by influencing cortical plasticity. However, in spite of the advances to date, little is known about the extent to which sensory input in the form of peripheral nerve stimulation can be successfully combined to physical training. A new emerging approach called constraint induced therapy (CIT) is an intensive functional motor training and has produced promising results in the field of stroke rehabilitation. CIT involves restraining the unaffected arm with a sling or glove combined with intense task-oriented therapy of the affected side for six hours daily during 2 weeks. This pilot study will evaluate the effectiveness of sustained peripheral nerve stimulation coupled with functional motor training to improve hand motor function. While the functional motor training follows identical principles of CIT, the length of daily training will be shortened to 4 hours daily and thus the PIs will refer to it in this proposal as a modified CIT. Preliminary data for this study demonstrated that peripheral nerve stimulation results in increased cortical motor excitability in normal subjects. In addition, learning and use-dependent plasticity can be substantially enhanced by a single session of 2 hours of peripheral nerve stimulation in chronic stroke patients. The goal of this study is to test the hypothesis that stroke patients treated with upper extremity peripheral nerve stimulation preceding CIT (intervention group) will have improved hand motor function compared to a group receiving lower extremity peripheral nerve stimulation and CIT (control group). The PIs also expect that the degree of motor functional improvement will correlate with the increase of cortical motor map measured by transcranial magnetic stimulation. The long-range goals are: (a) to maximize the restoration of hand motor function after stroke and (b) to determine the impact of this intervention in activities of daily living and quality of life. [unreadable] [unreadable] [unreadable] [unreadable]